Should nonalcoholic fatty liver disease be renamed?

BACKGROUND: None of the synonyms of nonalcoholic fatty liver disease (NAFLD) include clinical correlates nor do they mention insulin resistance, a recognized determinant of the etiopathogenesis and natural history of NAFLD. METHOD: The literature concerning the pathogenesis and definition of NAFLD is reviewed. RESULTS: The reasons why NAFLD should be renamed are: (a) clinically meaningful hepatic steatosis could be present at less than 5% triglyceride hepatic content; (b) steatosis is usually no longer observed in the most advanced forms of NAFLD ('cryptogenic cirrhosis'); (c) the concurrence of metabolic derangements could be more important than alcohol in the pathogenesis of alcoholic liver disease; (d) a concurrent metabolic etiology might worsen the course of chronic HCV and autoimmune hepatitis; (e) in NAFLD the liver is a target organ of the metabolic syndrome, a systemic subclinical inflammatory state. CONCLUSION: The introduction of a positive criterion also mentioned in its definition would benefit the diagnosis of NAFLD and of steatohepatitis observed in the setting of other liver diseases, help to estimate the risk of its progression and aid the treatment of metabolic (fatty) liver disorders. There is a compelling need for an experts' agreement on a new definition of insulin resistance/metabolic-related liver disease.     

Increased risk of cardiovascular disease in non-alcoholic fatty liver disease: causal effect or epiphenomenon?

Non-alcoholic fatty liver disease (NAFLD), comprising a spectrum of conditions ranging from pure steatosis to steatohepatitis and cirrhosis, has reached epidemic proportions and represents the most common cause of chronic liver disease in the community. The prevalence of NAFLD has been estimated to be between 20% and 30% in the general population, but this value is much higher (∼70–80%) in type 2 diabetic patients, who are also at higher risk of developing advanced fibrosis and cirrhosis. Increasing recognition of the importance of NAFLD and its strong relationship with the metabolic syndrome has stimulated an interest in the possible role of NAFLD in the development of cardiovascular disease (CVD). Several epidemiological studies indicate that NAFLD, especially in its more severe forms, is linked to an increased risk of CVD, independently of underlying cardiometabolic risk factors. This suggests that NAFLD is not merely a marker of CVD, but may also be actively involved in its pathogenesis. The possible molecular mediators linking NAFLD and CVD include the release of pro-atherogenic factors from the liver (C-reactive protein, fibrinogen, plasminogen activator inhibitor-1 and other inflammatory cytokines) as well as the contribution of NAFLD per se to whole-body insulin resistance and atherogenic dyslipidemia, in turn favouring CVD progression. The clinical impact of NAFLD on CVD risk deserves particular attention in view of the implications for screening and surveillance strategies in the growing number of patients with NAFLD. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Non-alcoholic fatty liver disease: a new and important cardiovascular risk factor?

Non-alcoholic fatty liver disease (NAFLD) affects up to a third of the population worldwide and may confer increased cardiometabolic risk with consequent adverse cardiovascular outcomes independent of traditional cardiovascular risk factors and the metabolic syndrome. It is characterized almost universally by insulin resistance and is strongly associated with type 2 diabetes and obesity. Non-alcoholic fatty liver disease is a marker of pathological ectopic fat accumulation combined with a low-grade chronic inflammatory state. This results in several deleterious pathophysiological processes including abnormal glucose, fatty acid and lipoprotein metabolism, increased oxidative stress, deranged adipokine profile, hypercoaguability, endothelial dysfunction, and accelerated progression of atherosclerosis. This ultimately leads to a dysfunctional cardiometabolic phenotype with cardiovascular mortality representing the main mode of premature death in NAFLD. This review is aimed at introducing NAFLD to the clinical cardiologist by discussing in-depth the evidence to date linking NAFLD with cardiovascular disease, reviewing the likely mechanisms underlying this association, as well as summarizing from a cardiologist's perspective, current and potential future treatment options for this increasingly prevalent disease.     

Physical activity support or weight loss counseling for nonalcoholic fatty liver disease?

AIM:To determine the clinical effectiveness of intense psychological support to physical activity(PA)in nonalcoholic fatty liver disease(NAFLD),compared with cognitive-behavioral treatment(CBT).METHODS:Twenty-two NAFLD cases received support to exercise,tailored to their motivational needs(PA group).The effects on body weight,physical fitness[6-min walk test,VO2max and the PA-rating(PA-R)questionnaire]and body fat(fatty liver indices and visceral adiposity index)were compared with data obtained in 44 NAFLD subjects enrolled in a CBT program for weight loss,after adjustment for propensity score,calculated on baseline data.Measurements were performed at baseline,at 4-mo and one-year follow-up.Changes in anthropometric,biochemical and PA parameters were tested by repeated measurement ANOVA.Outcome results were tested by logistic regression analysis.RESULTS:At the end of the intensive program,BMI was less significantly reduced in the PA group(-1.09±1.68 kg/m2 vs-2.04±1.42 kg/m2 in the CBT group,P=0.019)and the difference was maintained at 1-year follow-up(-0.73±1.63 vs-1.95±1.88,P=0.012)(ANOVA,P=0.005).PA-R was similar at baseline,when only 14%of cases in PA and 36%in CBT(P=0.120)recorded values≥3.At 4 mo,a PA-R≥3 was registered in 91%of PA and 46%of CBT,respectively(P<0.001)and PA-R≥5(up to 3 h/wk of moderate-toheavy intensity physical activity)was registered in 41%of PA and only 9%of CBT group(P<0.007).The6-min walk test increased by 139±26 m in PA and by only 43±38 m in CBT(P<0.001)and VO2max by8.2±3.8 mL/kg per minute and 3.3±2.7 mL/kg per minute,respectively(P<0.002).After adjustment for propensity,weight loss>7%was significantly associated with CBT group at one year(OR=6.21;95%CI:1.23-31.30),whereas PA-R>3 was associated with PA group(10.31;2.02-52.63).Liver enzymes decreased to values within normal limits in 36%of PA cases and61%of CBT(P<0.070).Estimated liver fat(Kotronen index)fell below the fatty liver threshold in 36%of PA and 34%and CBT cases at one-year(not different).Also the fatty liver index and the visceral adiposity index improved to a similar extent.CONCLUSION:Intensive psychological counseling for PA produces hepatic effects not different from standard CBT,improving physical fitness and liver fat independent of weight loss.Strategies promoting exercise are worth and effective in motivated patients,particularly in lean NAFLD patients where large weight loss cannot be systematically pursued.     

Valproic acid and nonalcoholic fatty liver disease: A possible association?

Valproic acid (VPA) is one of the most prescribed drugs in children with newly diagnosed epilepsy. Weight gain and obesity have been observed as side effects of VPA. These are often linked with other metabolic disturbances such as development of insulin resistance, dyslipidemia, metabolic syndrome (MetS) and non-alcoholic fatty liver disease or nonalcoholic fatty liver disease (NAFLD). NAFLD refers to a group of liver disorders with marked hepatic steatosis. It is associated with an increased incidence of cardiovascular diseases and overall reduced life expectancy. NAFLD occurs in 20%-25% of the general population and it is known to be the most common cause of chronic liver disease. NAFLD therefore represents a major public health issue worldwide. This study reviews and summarizes relevant literature that supports the existence of an association between VPA therapy and the development of NAFLD in children. Long-term VPA-therapy appears to be associated with an increased risk of developing NAFLD. Further studies are needed to clarify the pathogenic mechanisms that lie behind this association and to standardize the options for the use of this drug in overweight patients and in those with risks for developing MetS and NAFLD.     

Have guidelines addressing physical activity been established in nonalcoholic fatty liver disease?

The purpose of this review was to highlight, in relation to the currently accepted pathophysiology of non-alcoholic fatty liver disease (NAFLD), the known exercise habits of patients with NAFLD and to detail the benefits of lifestyle modification with exercise (and/or physical activity) on parameters of metabolic syndrome. More rigorous, controlled studies of longer duration and defined histopathological end-points comparing exercise alone and other treatment are needed before better, evidence-based physical activity modification guidelines can be established, since several questions remain unanswered.     

Redefining non-alcoholic fatty liver disease to metabolic associated fatty liver disease: Is this plausible?

Recently, a single letter change has taken the world by storm. A group of experts have developed a consensus to upgrade the term non-alcoholic fatty liver disease (NAFLD) to metabolic associated fatty liver disease (MAFLD), suggesting that MAFLD would more accurately reflect not only the disease pathogenesis but would also help in patient stratification for management with NAFLD. However, the difference of opinion exists, which has made the NAFLD vs MAFLD debate the current talk of the town. This review will focus on the plausibility and implications of redefining NAFLD as MAFLD.